Slow Decay Time Constants Research Articles

Hyaluronic acid mediated ZnO-NPs: In relation to electrical and photocatalytic activity for dye degradation

Various processes have been implemented to purify water; however, photocatalysis is comprehensively utilized in wastewater treatment and plays a significant role in water remediation. A photocatalyst is a nanostructured metal oxide ZnO nanoparticles, which boosts the reaction rate by its existence. ZnO nanoparticles show great performance in the absorption of various organic pollutants from wastewater. The objective of this research was to enhance the photocatalytic degradation performance of HA-added ZnO NPs using methylene blue as a model wastewater. Adjusting the main physical properties and photocatalytic efficiency of ZnO-NPs was performed using hyaluronic acid (HA), a natural bioactive stabilizer. The characterization of the fabricated ZnO-NPs samples with and without HA involved the utilization of FE-SEM, AFM, XRD, FTIR, PL, and I-V. As demonstrated by the FE-SEM analysis, ZnO formed rod-like structures, 3.0 % HA:ZnO exhibited cauliflower-like structures, and 5.0 % HA:ZnO displayed honeycomb-like structures. The X-ray diffraction (XRD) analysis demonstrated that the HA:ZnO nanoparticles exhibited hexagonal wurtzite structures. The average crystallite sizes of the ZnO, 3.0 % HA:ZnO, and 5.0 % HA:ZnO NPs were determined to be 25.20, 27.30, and 20.20 nm, respectively, using the XRD patterns. The surface area was 4.439, 2.987, and 5.204 m²/g of bare ZnO, 3.0 % HA:ZnO, and 5.0 % HA:ZnO-NPs were 4.439, 2.987, and 5.204 m2/g, respectively. It is very likely that there are two different decay and/or capture mechanisms in the emission spectra because the TRPL decay profile behaves in a double-exponential way. The fast decay time constant (τ1) was 212 ps for bare ZnO and 3.0 % HA:ZnO NPs and 231 ps for 5.0 % HA:ZnO NPs. The slow decay time constant (τ2) has a similar pattern, with values of 3.716, 2.836, and 2.984 ns. The specific contact resistance values of the ZnO NPs increased from 0.113 to 45.624 ( × 105 Ω cm2) as a function of the HA concentration, as evidenced by the results of the electrical studies. The outcomes of this research present comprehensive information on noble-modified ZnO-NP materials containing HA for direct applications in electronic materials and photocatalytic degradation of organic waste in water.

Analysis of signal waveform from a midsize liquid argon detector

The midsize single-phase liquid argon prototype detector, operating at the surface laboratory, is designed to measure scintillation light emitted by the liquid argon (LAr). The detector employs 42 8-inch photomultiplier tubes (PMT) to collect the light. By analyzing the waveform of the signal, important detector characteristics such as the slow decay time constant that characterizes the purity of the liquid argon can be obtained. To describe the signal waveform, a model, which takes into account the liquid argon emission decay times together with the TPB re-emission process as well as the signal reflection effects, is used. The TPB re-emission process is introduced using a three-exponential time structure. Additionally, experimental results provide comprehensive validation for a post-peak hump structure, which is attributed to signal reflection.

Radiation Damage in Polyethylene Naphthalate Thin-Film Scintillators.

This paper describes the scintillation features and the radiation damage in polyethylene naphthalate 100 µm-thick scintillators irradiated with an 11 MeV proton beam and with a 1 MeV electron beam at doses up to 15 and 85 Mrad, respectively. The scintillator emission spectrum, optical transmission, light yield loss, and scintillation pulse decay times were investigated before and after the irradiation. A deep blue emission spectrum peaked at 422 nm, and fast and slow scintillation decay time constants of the order of 1–2 ns and 25–30 nm, respectively, were measured. After irradiation, transmittance showed a loss of transparency for wavelengths between 380 and 420 nm, and a light yield reduction of ~40% was measured at the maximum dose of 85 Mrad.

Elucidating the mechanism of potential induced degradation delay effect by ultraviolet light irradiation for p-type crystalline silicon solar cells

A mechanism of potential induced degradation (PID) delay effect by ultraviolet (UV) light irradiation during PID test for p-type crystalline silicon (c-Si) solar cells was proposed in this work. The degradation rate of the solar cell performances is slowed down by the UV light irradiation in the 300–390 nm wavelength range during PID test. The conductivity increase of the silicon nitride (SiNx) anti-reflection coating (ARC) layer on the solar cell surface under UV light irradiation during PID tests, which relates to the mechanism preventing the penetration of sodium ions into the active cell layer, induces the PID delay effect for the p-type c-Si solar cells. The PID delay effect was also analyzed by a microwave photo-conductance decay (μ-PCD) technique in this work. The reduction behavior of the components in the μ-PCD signal curves including rapid (τ1) and slow (τ2) decay time constants and the effective lifetime (τeff) presents a good correlation with the performance degradation behavior of the solar cells over PID test duration. Moreover, the reduction rate of these components is also slowed down under the UV light irradiation in the 300–390 nm wavelength range during PID tests. Notably, their reduction behavior was compatible with the mechanism of the conductivity increase of the SiNx ARC layer under UV light irradiation.

Exploring a new method for quantitative sodium MRI in the human upper leg with a surface coil and symmetrically arranged reference phantoms.

The aim of this study is to validate and evaluate the reproducibility of a new setup for the quantification of the tissue sodium concentration (TSC) in the human upper leg muscles with sodium MRI at 3 Tesla. This setup is making use of an emit and receive single loop surface coil together with a set of square, symmetrically arranged reference phantoms. As a second aim, the performances of two MRI protocols for the TSC quantification in the upper leg muscles are compared: one using an ultra-short echo time (UTE) 3-dimensional radial sequence (UTE-protocol), and the other one using standard gradient echo sequence (GRE-protocol). A validation test of the quantification of sodium concentration is performed in phantoms. The bias of the method is estimated and compared between both protocols. The reproducibility of TSC quantification is assessed in phantoms by the coefficient of variation (CV) and compared between both protocols. The reproducibility is also assessed in 11 health volunteers. Signal to noise ratio (SNR) maps are acquired in phantoms with both protocols in order to compare the resulting SNR. The apparatus and post processing were successfully implemented. The bias of the method was smaller than 10% in phantoms (excepted for Na concentration of 10 mmol/L when using the GRE protocol). The reproducibility of the method using symmetrically arranged phantoms was high in phantoms and humans (CV <5%). The GRE-protocol leads to a better SNR than the UTE-protocol in 2D images. The use of symmetrically arranged reference phantoms lead to reproducible results in phantoms and humans. Sodium imaging in the human upper leg with a single loop surface coil should be performed with a standard 2-dimensional GRE protocol if an optimal SNR is needed. However, the quantification of the fast and slow decay time constants of the sodium signal, which plays a role in the TSC quantification, still has to be done with a UTE sequence. Moreover, the quantification of sodium concentration is more accurate with the UTE protocol for small sodium concentrations (<20 mmol).

Hot electron mediated enhancement in the decay rates of persistent photocurrent in gold nanoparticles embedded indium oxide films

A major factor that hinders the realization of indium oxide (IO) as a potential gas/photosensor is the response time, which is quite poor. For instance, the photoresponse of dc sputtered IO films under UV and sub-bandgap illumination is known to exhibit bi-exponential decay with fast (10–100 min) and slow (∼3000 min) time constants. We demonstrate here that the response time can be greatly improved by the hot carriers generated through localized surface plasmon decay. Our study shows that when IO films are incorporated with gold nanoparticles (AuNPs), the fast and slow decay time constants are reduced by a factor of 20 and 30, respectively, at excitation wavelengths close to the localized surface plasmon resonance (LSPR) wavelength. We also show the possibility to achieve wavelength tunable reduction in the time constants by tuning the LSPR wavelength. We attribute the changes to the strong enhancement in the recombination rates facilitated by plasmon decay-mediated excess hot electrons injected into the conduction band of IO. We use a simple analytical model to explain the role of plasmon-mediated hot electrons in enhancing the recombination rate. We believe that the present results are of great significance to improve the response time of metal oxide based photodetectors/sensors, in general, since the underlying physical process depends primarily on the plasmonic nature of the AuNPs.

Granule cell excitability regulates gamma and beta oscillations in a model of the olfactory bulb dendrodendritic microcircuit.

Odors evoke gamma (40-100 Hz) and beta (20-30 Hz) oscillations in the local field potential (LFP) of the mammalian olfactory bulb (OB). Gamma (and possibly beta) oscillations arise from interactions in the dendrodendritic microcircuit between excitatory mitral cells (MCs) and inhibitory granule cells (GCs). When cortical descending inputs to the OB are blocked, beta oscillations are extinguished whereas gamma oscillations become larger. Much of this centrifugal input targets inhibitory interneurons in the GC layer and regulates the excitability of GCs, which suggests a causal link between the emergence of beta oscillations and GC excitability. We investigate the effect that GC excitability has on network oscillations in a computational model of the MC-GC dendrodendritic network with Ca(2+)-dependent graded inhibition. Results from our model suggest that when GC excitability is low, the graded inhibitory current mediated by NMDA channels and voltage-dependent Ca(2+) channels (VDCCs) is also low, allowing MC populations to fire in the gamma frequency range. When GC excitability is increased, the activation of NMDA receptors and other VDCCs is also increased, allowing the slow decay time constants of these channels to sustain beta-frequency oscillations. Our model argues that Ca(2+) flow through VDCCs alone could sustain beta oscillations and that the switch between gamma and beta oscillations can be triggered by an increase in the excitability state of a subpopulation of GCs.

Granule cell excitability mediates gamma and beta oscillations in a model of the dendrodendritic microcircuit

Odors evoke gamma (60 - 100 Hz) and beta (20 - 30 Hz) oscillations in the local field potential (LFP) of the rat olfactory bulb (OB). These oscillations arise from activity in the dendrodendritic microcircuit between excitatory mitral cells (MCs) and inhibitory granule cells (GCs) [1]. When cortical feedback inputs to the OB are blocked, beta oscillations are extinguished while gamma oscillations persist [2]. Much of this cortical feedback targets inhibitory interneurons in the GC layer and regulates the excitability of GCs [3], which suggests a causal link between the emergence of beta oscillations and the GC excitability. We investigate the effect that GC excitability has on network oscillations in a biophysical model of the MC-GC dendrodendritic network with graded inhibition. When GC excitability is low, there is transient activation of NMDAR channels by AMPARs, which produces fast inhibitory pulses in the gamma frequency range. When GC excitability is increased, the activation of NMDARs and other VDCCs is prolonged, allowing the slow decay time constants of these channels to drive beta frequency oscillations. The power of the beta oscillation peaks when inhibitory and excitatory currents onto MCs are balanced, which could explain the relationship between beta power and odor volatility measured experimentally [4].

Correlating the Luminosity Parameters to Pulse Shape Discrimination

Monte Carlo simulations were used to investigate the correlation between luminosity parameters and pulse shape discrimination (PSD) and subsequently compared with experimental results from CsI:Tl. Luminosity intensity parameters Af, As (fast and slow initial luminosities) and temporal luminosity parameters τf, τs (fast and slow decay time constants) of a dual decay mode scintillator were applied to create a dynamic model with Crystal Ball simulation system. The simulated pulses were analyzed with charge comparison (CC) and constant time discrimination (CTD) PSD methods followed by quantification of the histogrammed pulse data with Figure of Merit (FoM) and spillover (pulse misclassification). Performance in terms of FoM and spillover is compared with that of fixed reference pulses set at (Af τf/As τs)γ = 1 and (Af τf/As τs)γ = 0.1. For the CC method, independent of the reference pulse characteristics [(Af τf/As τs)γ = 1 or = 0.1], τs is the most influential parameter for PSD as compared with Af, As, and τf. For the CTD method, Af and As are seen to have less influence over the PSD compared to τf and τs when (Af τf/As τs)γ = 1 and τf is the most influential parameter for both reference pulses. Using both methods with either reference pulse applied, the scintillator having luminosity parameters such that is classified as having poor PSD. Excellent correlation is observed between the simulation and the experimental results with CsI:Tl, which is known for very good α/β(γ) pulse shape discrimination. This study is useful for describing how the luminosity parameters affects PSD.

Role of TRP channels in dendritic integration and subthreshold membrane potential plateaus

Cortical as well as subcortical neurons display plateau properties [1]. The plateaus may be voltage and/or calcium gated and depend on Na, Ca or mixed cation (TRP) currents. Depending on the nature of the synaptic input, neurons may respond by entering one of several multiple stable states, in the form of either subthreshold or persistent firing. We have studied the activation of a TRP current, in which synaptic excitatory input activates metabotropic glutamate receptors in turn leading to a TRP-mediated slow EPSP, both experimentally [2] and computationally [3]. In the computational work we have studied the contribution of the TRP current on dendritic integration of input of low (1-10 Hz) frequency. The model is based on a CA1 pyramidal cell model [4] developed to study dendritic processing. The spatial compartmentalization had been obtained from a digitized neuron and contains 183 compartments. It includes ion channels described by a Hodgkin-Huxley formalism and has the following channels: Na, NaP, CaR, CaT, CaL, Kdr, KA, KM, K(Ca)BK, K(Ca)slow, Kleak, h. To this model we added models for a metabotropic glutamate receptor as well as a TRP channel, the latter being adapted from a CAN channel model. Continuing our computational work, we have recently studied how the dendritic integration properties depend on the time constant of the calcium activating the TRP-current. In the model calcium comes from L-type Cav1.3 channels with a low threshold but there may also be contributions from T-type channels. We find that the effective integration time constant, the decay time constant of the neuronal membrane, increases when the amplitude of the calcium concentration increases. Moreover, recent experimental work [5] has shown that the decay time constant of calcium increases as a result of increased calcium concentration. This prompted us to study effects of adding a slower decay time constant in addition to the one present in the model used so far. Intriguingly, we find that a stable subthreshold plateau appears when a slower (200 ms) calcium decay time constant is present but not when only the original faster (30 ms) is present. This plateau of the resting potential is stable for weaker synaptic excitatory or inhibitory input, but stronger input can switch the membrane between the two levels, see figure ​figure1.1. We find that the subthreshold plateau is essentially local to individual dendritic branches, and that the cell enters a persistent spiking [1] mode when several branches enters plateau mode. This bistability in membrane potential due to intrinsic conductances may be compared to the network driven changes of subthreshold membrane potential during cortical up and down states, suggested to switch the neuron between different modes of integration/operation. Figure 1 The membrane voltage (Vm) is resting close to -70 mV. At the arrival of an excitatory synaptic stimulus, Vm enters a more depolarized, subthreshold plateau, which is stable to weak inhibitory input (t = 3000 ms). Vm returns to its resting state only if ...

Different effects of α-chloralose on spontaneous and evoked GABA release in rat hippocampal CA1 neurons

The effects of α-chloralose on presynaptic GABA A receptors were investigated with respect to spontaneous and evoked GABAergic transmission (sIPSCs and eIPSCs) in rat hippocampal CA1 pyramidal neurons. sIPSCs were recorded in mechanically dissociated CA1 neurons with intact GABAergic terminals, namely the “synaptic bouton preparation.” eIPSCs were elicited by focal electrical stimuli of a single GABAergic bouton on an isolated CA1 neuron using the whole-cell patch recording configurations under voltage-clamp condition. We found that α-chloralose potentiated the exogenous GABA-induced Cl − response in a concentration dependent manner, and the drug itself induced Cl − response at high concentrations (>100 μM). α-Chloralose at low concentrations (3–10 μM) increased sIPSC frequency without affecting the current amplitude and kinetics, but prolonged the slow current decay time constant ( τ s) at concentrations greater than 30 μM without changing either current amplitude or frequency. α-Chloralose at 10 μM enhanced amplitude of eIPSCs and decreased the failure rate (Rf), but at 30 μM decreased the amplitude and increased the Rf. Pretreatment with bumetanide, a blocker of NKCC-1, completely prevented the 30 μM α-chloralose-induced inhibition on eIPSC amplitude and Rf. These results suggest that α-chloralose activates GABA A receptors on GABAergic presynaptic nerve terminals and depolarizes the terminals, mediating presynaptic inhibition or autoregulation, in a concentration-dependent manner. In addition, α-chloralose at high concentrations activates not only extrasynaptic GABA A receptors on the postsynaptic soma membrane but also synaptic GABA A receptors resulting in prolongation of current decay phase. Thus α-chloralose induces complex and differential modulation of sIPSCs and eIPSCs in a concentration dependent manner.

Electron emission properties of two-phase argon and argon-nitrogen avalanche detectors

Electron emission properties of two-phase Ar avalanche detectors are studied. The detectors investigated comprised a liquid Ar or Ar+N2 layer followed by a multi-GEM multiplier operated in the saturated vapour at 84 K. Two components of the electron emission through the liquid-gas interface were observed: fast and slow. In Ar, the slow emission component dominated even at higher fields, reaching 2 kV/cm. In Ar+N2 on the contrary, the fast emission component dominated at higher fields, the slow component being disappeared. This is explained by the electron backscattering effect in the gas phase. The slow component decay time constant was inversely proportional to the electric field, which is compatible with thermionic emission model. The electron emission efficiencies in two-phase Ar and Ar+N2 were estimated to be close to each other.

NF-κB Mediated Enhancement of Potassium Currents by the Chemokine CXCL1/Growth Related Oncogene in Small Diameter Rat Sensory Neurons

BackgroundInflammatory processes play important roles in both neuropathic and inflammatory pain states, but the effects of inflammation per se within the sensory ganglia are not well understood. The cytokine growth-related oncogene (GRO/KC; CXCL1) shows strong, rapid upregulation in dorsal root ganglion (DRG) in both nerve injury and inflammatory pain models. We examined the direct effects of GRO/KC on small diameter DRG neurons, which are predominantly nociceptive. Whole cell voltage clamp technique was used to measure voltage-activated potassium (K) currents in acutely cultured adult rat small diameter sensory neurons. Fluorescently labeled isolectin B4 (IB4) was used to classify cells as IB4-positive or IB4-negative.ResultsIn IB4-negative neurons, voltage-activated K current densities of both transient and sustained components were increased after overnight incubation with GRO/KC (1.5 nM), without marked changes in voltage dependence or kinetics. The average values for the slow and fast decay time constants at 20 mV were unchanged by GRO/KC. The amplitude of the fast inactivating component increased significantly with no large shifts in the voltage dependence of inactivation. The increase in K currents was completely blocked by co-incubation with protein synthesis inhibitor cycloheximide (CHX) or NF-κB inhibitors pyrrolidine dithiocarbamate (PDTC) or quinazoline (6-Amino-4-(4-phenoxypheny lethylamino;QNZ). In contrast, the voltage-activated K current of IB4-positive neurons was unchanged by GRO/KC. GRO/KC incubation caused no significant changes in the expression level of eight selected voltage-gated K channel genes in quantitative PCR analysis.ConclusionThe results suggest that GRO/KC has important effects in inflammatory processes via its direct actions on sensory neurons, and that activation of NF-κB is involved in the GRO/KC-induced enhancement of K currents.

Measurement of decay time of liquid scintillator

In this paper we describe a single photon method to measure the decay time of two kinds of homemade liquid scintillator. We find that the fast and slow decay time constants of these two samples, with 5 cm diameter and 4 cm height, are about ∼ 4 ns and ∼ 17 ns , respectively. These results are checked through a reference measurement by recording the scintillation pulse shapes at the output of a fast response PMT directly by a digital oscilloscope. The time responses of these two samples are as good as those of commercial liquid scintillator.

Characterization of electron transfer from CdSe quantum dots to nanostructured TiO 2 electrode using a near-field heterodyne transient grating technique

The ultrafast carrier dynamics of the CdSe QDs adsorbed on a nanostructured TiO 2 electrode and on a glass substrate were studied using a near-field heterodyne detection transient grating (NF-HD-TG) method. Two decay processes were observed in the TG responses. The fast decay time constants τ 1 were the same (2.3 ps) for these two kinds of substrates, corresponding to the photoexcited hole relaxation in the CdSe QDs. However, the slow decay time constants τ 2 were very different for these two kinds of substrates, reflecting the photoexcited electron relaxation (i.e., trapping and/or transfer). Since no electron transfer from the CdSe QDs to the glass substrate could occur, we could estimate the electron transfer rate from the CdSe QDs into the nanostructured TiO 2 electrode to be approximately 5.4 × 10 9 s − 1 using the values of τ 2 detected for these two kinds of substrates.

Function of Chlorophyll d in Reaction Centers of Photosystems I and II of the Oxygenic Photosynthesis of Acaryochloris marina

Reaction center chlorophylls (Chls) in photosystems II and I were studied in the isolated thylakoid membranes of a cyanobacterium, Acaryochloris marina, which contains Chls d and a as the major and minor pigments, respectively. The membranes contained PS I and II complexes at a 1.8:1 molar ratio on the basis of the spin densities on the tyrosine D radical and the photo-oxidized PS I primary donor (P740+). In the presence of ferricyanide, laser excitation induced bleach at 725 nm that recovered with time constants of 25 micros and 1.2 ms. The signal, designated P725, was suppressed by PS II inhibitors DCMU and hydroxylamine. The P725 spectrum was tentatively assigned to the absorption changes of the special pair Chl d, the accessory Chl d, and the acceptor pheophytin a in PS II. The addition of ascorbate induced the additional signal with a slow decay time constant of 4.5 ms. This signal showed a broad bleach at 740 nm and shift-type absorption changes at around 707 and 685 nm, which were assigned to the absorption changes of PS I special pair of Chl d (P740), the accessory Chl d, and the primary acceptor Chl a (A0), respectively. Mechanisms and the evolution of the Chl-d based reaction centers using far-red light are discussed together with the amino acid sequences of PS II D1 and D2 proteins.

Site specific Eu3+ stimulated emission in GaN host

We report the observation of site-specific Eu3+ stimulated emission in GaN:Eu laser structures. Two main Eu sites have been identified from emission peaks associated with the D05→F27 transition during above band gap optical pumping with a pulsed N2 laser (337nm): (a) Eux emitting at ∼620nm—present in short cavities (∼100μm), exhibiting stimulated (side) emission threshold and a fast decay time constant (30–35μs); (b) Euy emitting at ∼621nm—present in long cavities (∼7mm) and in surface emission, exhibiting no stimulated emission threshold and a slow decay time constant (150–250μs).

Are Altered Excitatory Synapses Found in Neuronal Migration Disorders?

Physiological and Morphological Characterization of Dentate Granule Cells in the p35 Knock-out Mouse Hippocampus: Evidence for an Epileptic Circuit Patel LS, Wenzel HJ, Schwartzkroin PA J Neurosci 2004;24:9005–9014 There is a high correlation between pediatric epilepsies and neuronal migration disorders. What remains unclear is whether intrinsic features of the individual dysplastic cells give rise to heightened seizure susceptibility, or whether these dysplastic cells contribute to seizure activity by establishing abnormal circuits that alter the balance of inhibition and excitation. Mice lacking a functional p35 gene provide an ideal model in which to address these questions, because these knockout animals not only exhibit aberrant neuronal migration but also demonstrate spontaneous seizures. Extracellular field recordings from hippocampal slices, characterizing the input–output relation in the dentate, revealed little difference between wild-type and knockout mice under both normal and elevated extracellular potassium conditions. However, in the presence of the GABAA antagonist bicuculline, p35 knockout slices, but not wild-type slices, exhibited prolonged depolarizations in response to stimulation of the perforant path. No significant differences were found in the intrinsic properties of dentate granule cells (i.e., input resistance, time constant, action-potential generation) from wild-type versus knockout mice. However, antidromic activation (mossy fiber stimulation) evoked an excitatory synaptic response in more than 65% of granule cells from p35 knockout slices that was never observed in wild-type slices. Ultrastructural analyses identified morphological substrates for this aberrant excitation: recurrent axon collaterals, abnormal basal dendrites, and mossy fiber terminals forming synapses onto the spines of neighboring granule cells. These studies suggest that granule cells in p35 knockout mice contribute to seizure activity by forming an abnormal excitatory feedback circuit. Prolonged NMDA-mediated Synaptic Response, Altered Ifenprodil Sensitivity, and Generation of Epileptiform-like Events in a Malformed Hippocampus of Rats Exposed to Methylazoxymethanol in Utero Calcagnotto ME, Baraban SC J Neurophysiol 2005 [Epub ahead of print] Cortical malformations are often associated with refractory epilepsy and cognitive deficit. Clinical and experimental studies have demonstrated an important role for glutamate-mediated synaptic transmission in these conditions. With whole-cell voltage-clamp techniques, we examined evoked glutamate-mediated excitatory postsynaptic currents (eEPSCs) and responses to exogenously applied glutamate on hippocampal heterotopic cells in an animal model of malformation (i.e., rats exposed to methylazoxymethanol [MAM] in utero). Analysis of eEPSCs revealed that the late N-methyl-D-aspartate (NMDA) receptor–mediated eEPSC component was significantly increased on heterotopic cells compared with age-matched normotopic pyramidal cells. At a holding potential of +40 mV, heterotopic cells also exhibited eEPSCs with a slower decay-time constant. No differences in the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) component of eEPSCs were detected. In 23% of heterotopic pyramidal cells, electrical stimulation evoked prolonged burstlike responses. Focal application of glutamate (10 m M) targeted to different sites near the heterotopia also evoked epileptiform-like bursts on heterotopic cells. Ifenprodil (10 μM), an NR2B subunit antagonist, only slightly reduced the NMDA receptor–mediated component and amplitude of eEPSCs on heterotopic cells (MAM) but significantly decreased the late component and peak amplitude of eEPSCs in normotopic cells (Control). Our data demonstrate a functional alteration in the NMDA-mediated component of excitatory synaptic transmission in heterotopic cells and suggest that this alteration may be attributable, at least in part, to changes in composition and function of the NMDAR subunit. Changes in NMDA-receptor function may directly contribute to the hyperexcitability and cognitive deficits reported in animal models and patients with brain malformations.

Prolonged NMDA-Mediated Responses, Altered Ifenprodil Sensitivity, and Epileptiform-Like Events in the Malformed Hippocampus of Methylazoxymethanol Exposed Rats

Cortical malformations are often associated with refractory epilepsy and cognitive deficit. Clinical and experimental studies have demonstrated an important role for glutamate-mediated synaptic transmission in these conditions. Using whole cell voltage-clamp techniques, we examined evoked glutamate-mediated excitatory postsynaptic currents (eEPSCs) and responses to exogenously applied glutamate on hippocampal heterotopic cells in an animal model of malformation i.e., rats exposed to methylazoxymethanol (MAM) in utero. Analysis revealed that the late N-methyl-D-aspartate (NMDA) receptor-mediated eEPSC component was significantly increased on heterotopic cells compared with age-matched normotopic pyramidal cells. At a holding potential of +40 mV, heterotopic cells also exhibited eEPSCs with a slower decay-time constant. No differences in the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) component of eEPSCs were detected. In 23% of heterotopic pyramidal cells, electrical stimulation evoked prolonged burst-like responses. Focal application of glutamate (10 mM) targeted to different sites near the heterotopia also evoked epileptiform-like bursts on heterotopic cells. Ifenprodil (10 microM), an NR2B subunit antagonist, only slightly reduced the NMDA receptor (NMDAR)-mediated component and amplitude of eEPSCs on heterotopic cells (MAM) but significantly decreased the late component and peak amplitude of eEPSCs in normotopic cells (control). Our data demonstrate a functional alteration in the NMDA-mediated component of excitatory synaptic transmission in heterotopic cells and suggest that this alteration may be attributable, at least in part, to changes in composition and function of the NMDAR subunit. Changes in NMDAR function may directly contribute to the hyperexcitability and cognitive deficits reported in animal models and patients with brain malformations.

Excitatory synaptic transmission in the lateral and central amygdala.

The amygdala plays a major role in the acquisition and expression of fear conditioning. NMDA receptor-dependent synaptic plasticity within the basolateral amygdala has been proposed to underlie the acquisition and possible storage of fear memories. Here the properties of fast glutamatergic transmission in the lateral and central nuclei of the amygdala are presented. In the lateral amygdala, two types of neurons, interneurons and projection neurons, could be distinguished by their different firing properties. Glutamatergic inputs to interneurons activated AMPA receptors with inwardly rectifying current-voltage relations (I-Vs), whereas inputs to projection neurons activated receptors that had linear I-Vs, indicating that receptors on interneurons lack GluR2 subunits. Inputs to projection neurons formed dual component synapses with both AMPA and NMDA components, whereas at inputs to interneurons, the contribution of NMDA receptors was very small. Neurons in the central amygdala received dual component glutamatergic inputs that activated AMPA receptors with linear I-Vs. NMDA receptor-mediated EPSCs had slow decay time constants in the central nucleus. Application of NR2B selective blockers ifenprodil or CP-101,606 blocked NMDA EPSCs by 70% in the central nucleus, but only by 30% in the lateral nucleus. These data show that the distribution of glutamatergic receptors on amygdalar neurons is not uniform. In the lateral amygdala, interneurons and pyramidal neurons express AMPA receptors with different subunit compositions. Synapses in the central nucleus activate NMDA receptors that contain NR1 and NR2B subunits, whereas synapses in the lateral nucleus contain receptors with both NR2A and NR2B subunits.